The direct intermolecular regiospecific and highly enantioselective a-allylic alkylation of linear aldehydes by combination of achiral bench stable Pd(0) complexes and simple chiral amines as co-catalysts is disclosed. The co-catalytic asymmetric chemoselective and regiospecific a-allylic alkylation reaction is linked in tandem with in situ reduction to give the corresponding 2-alkyl alcohols with high enantiomeric ratios (up to 98:2 er). It is also an expeditious entry to valuable 2-alkyl substituted hemiacetals and 2-alkyl-butane-1,4-diols.

The first direct intermolecular regiospecific and highly enantioselective a-allylic alkylation of linear aldehydes by a combination of achiral bench-stable Pd0 complexes and simple chiral amines as co-catalysts is disclosed. The co-catalytic asymmetric chemoselective and regiospecific a-allylic alkylation reaction is linked in tandem with in situ reduction to give the corresponding 2-alkyl alcohols with high enantiomeric ratios (up to 98:2 e.r.; e.r.=enantiomeric ratio). It is also an expeditious entry to valuable 2-alkyl substituted hemiacetals, 2-alkyl-butane-1,4-diols, and amines. The concise co-catalytic asymmetric total syntheses of biologically active natural products (e.g., Arundic acid) are disclosed.

Allylic alcohols can be isomerised into carbonyl compounds by transition metal complexes. In the last few years, catalyst design and development have resulted in highly efficient isomerisations under mild reaction conditions, including enantioselective versions. In addition, the isomerisation of allylic alcohols has been combined with C-C bond forming reactions when electrophiles such as aldehydes or imines were present in the reaction mixture. Also, C-F bonds can be formed when electrophilic fluorinating reagents are used. Thus, allylic alcohols can be treated as latent enol(ate)s. In this article, we highlight the latest developments concerning the isomerisation of allylic alcohols into carbonyl compounds, focusing in particular on tandem isomerisation/C-C or C-heteroatom bond formation processes. Significant attention is given to the mechanistic aspects of the reactions.

Pd-catalyzed allylic C-H trifluoroacetoxylation of substituted alkenes was performed using PhI(OCOCF3)(2) as the oxidant and acyloxy source. Trifluoroacetoxylation of monosubstituted cyclopentenes and cyclohexenes proceeds with excellent regio- and diastereoselectivity. Studies with one of the possible (eta(3)-allyl)Pd(II) intermediates suggest that the reaction proceeds via stereoselective formation of Pd(IV) intermediates and subsequent stereo- and regioselective reductive elimination of the product.

This thesis reports on unsaturated silicon compounds, as well as excursions from these into germanium chemistry, single molecule electronics, and silyl protective group chemistry. Both experimental and computational investigations were performed.

Potassium germenolates were synthesized through reactions of tris(timethylsilyl) substituted acyl- and carbamylgermanes with potassium tert-butoxide. The potassium germenolates calculated by density functional theory have pyramidal structures at the Ge atoms, similar to the Si in the corresponding potassium silenolates, indicating negative charge on germanium rather than on oxygen. Germenolates also display germyl anion-like reactivity instead of germene-like reactivity as they are alkylated at Ge and initiate anionic polymerization of dienes rather than form [4+2] cycloadducts. The NMR chemical shifts reveal more negative charge at Ge in germenolates than at Si in analogous silenolates.

Computations indicate that silabenzenes and silapyridines are reachable via [1,3]-silyl shifts from cyclic conjugated acylsilanes. Differently sized substituents were considered to prevent dimerizations, and 1-triisopropylsilyl-2-triisopropylsiloxy-6-tert-butylsilabenzene is a good synthetic target. Computations also show that silaphenolates are species with negative charge primarily localized at oxygen atom. Their planar structures, bond lengths, and NICS values reveal significant influence of aromaticity. Electrostatic repulsion should increase their stability, however, steric bulk is also important.

Furthermore, it was found computationally that [1,3]-silyl shift from an acylsilane to a silene can function as a molecular switch reaction. Conductance calculations support this proposition.

Finally, tris(trimethylsilyl)silylmethaneamide (hypersilylamide) together with catalytic amounts of triflic acid were found to be efficient for protection of a range of alkyl and aryl alcohols and thiols in good to excellent yields. The protocol can be used to protect the less hindered OH group of a diol and has a broad functional group tolerance. A catalytic cycle is proposed. Hypersilyl protected alcohols and thiols are deprotected efficiently under photolytic conditions.

Tris(trimethylsilyl)silyl-N,N-dimethylmethaneamide, herein named hypersilylamide, is a convenient and efficient source of the hypersilyl group in the first widely applicable acid catalyzed protocol for silyl group protection of primary, secondary, tertiary alkyl as well as aryl alcohols and thiols in high yields. The sole by-product is N,N-dimethylformamide (DMF) and a range of solvents can be used, including DMF. A high selectivity in the protection of diols can be achieved, also for diols with very small differences in the steric demands at the two hydroxyl groups. Moreover, in the protection of equivalent alcohol and thiol sites the protection of the alcohol is faster, allowing for selective protection in high yields. Quantum chemical calculations at the M062X hybrid meta density functional theory level give insights on the mechanism for the catalytic process. Finally, the hypersilyl group is easily removed from all protected alcohols and thiols examined herein by irradiation at 254 nm.

A new [60]fullerene dumbbell consisting of two fulleropyrrolidines connected to a central ferrocene unit by amide linkages has been prepared and fully characterized by elemental analysis, 1H NMR, UV/Vis, fluorescence and mass spectrometry. The electrochemical properties as determined by cyclic voltammetry show ground state electronic communication between the ferrocene and the fullerene units. In addition, the preparaton of a ferrocene building block for an alternative linking approach is presented.

Salt-bridge interactions between acidic and basic amino acids contribute to the structural stability of proteins and to protein-protein interactions. A conserved salt-bridge is a canonical feature of the alpha-defensin antimicrobial peptide family, but the role of this common structural element has not been fully elucidated. We have investigated mouse Paneth cell alpha-defensin cryptdin-4 (Crp4) and peptide variants with mutations at Arg(7) or Glu(15) residue positions to disrupt the salt-bridge and assess the consequences on Crp4 structure, function, and stability. NMR analyses showed that both (R7G)-Crp4 and (E15G)-Crp4 adopt native-like structures, evidence of fold plasticity that allows peptides to reshuffle side chains and stabilize the structure in the absence of the salt-bridge. In contrast, introduction of a large hydrophobic side chain at position 15, as in (E15L)-Crp4 cannot be accommodated in the context of the Crp4 primary structure. Regardless of which side of the salt-bridge was mutated, salt-bridge variants retained bactericidal peptide activity with differential microbicidal effects against certain bacterial cell targets, confirming that the salt-bridge does not determine bactericidal activity per se. The increased structural flexibility induced by salt-bridge disruption enhanced peptide sensitivity to proteolysis. Although sensitivity to proteolysis by MMP7 was unaffected by most Arg(7) and Glu(15) substitutions, every salt-bridge variant was degraded extensively by trypsin. Moreover, the salt-bridge facilitates adoption of the characteristic alpha-defensin fold as shown by the impaired in vitro refolding of (E15D)-proCrp4, the most conservative salt-bridge disrupting replacement. In Crp4, therefore, the canonical alpha-defensin salt-bridge facilitates adoption of the characteristic alpha-defensin fold, which decreases structural flexibility and confers resistance to degradation by proteinases.

An important feature of the synthesis of salinosporamide A. a potent proteasome inhibitor, is the establishment of the quaternary stereocenter at C3. A new route has been developed based on the methylation of a functionalized pyrrolidinone. Direct methylation reaction led to the unwanted diastereomer: however, by means of a Corey-Chaykovsky reaction followed by LiAlH4 epoxide opening, the desired alcohol was obtained. The pyrrolidinone was elaborated through a key allylation reaction between a tertiary allyltitanium reagent and an aldehyde bearing a spiroketal moiety in alpha-position.

In the first part, the development of an efficient method for the synthesis of β-hydroxy ketones (aldols) and β-amino ketones (Mannich products) from allylic alcohols and aldehydes is described. These reactions use Ru(η5-C5Ph5)(CO)2Cl as the catalyst. The reaction parameters were optimised in order to suppress the formation of undesired by-products. Neutral and mild reaction conditions enabled the synthesis of a variety of aldol products in up to 99% yield, with a good syn/anti ratio. The influence of the stereoelectronic properties of the catalyst on the reaction outcome was also studied. Based on the results obtained, a plausible reaction mechanism has been proposed, involving as the key steps the 1,4-addition of hydride to α,β-unsaturated ketones and the formation of ruthenium (Z)-enolates.

In the second part of this thesis, aruthenium-catalysed tandem isomerisation/C-H activation reaction is presented. A number of ruthenium complexes, phosphine ligands, and additives were evaluated in order to establish the optimal reaction conditions. It was found that the use of a stable ruthenium catalyst, Ru(PPh3)3Cl2, together with PtBu3 and HCO2Na resulted in an efficient tandem transformation. Using this procedure, a variety of ortho-alkylated ketones were obtained in excellent yields. Moreover, homoallylic alcohols could also be used as starting materials for the reaction, which further expands the substrate scope. Mechanistic investigations into the isomerisation part of the process were carried out.

The last project described in the thesis deals with the design and preparation of novel bifunctional iridium complexes containing an N-(2-hydroxy-isobutyl)-N-Heterocyclic carbene ligand. These complexes were used as catalysts to alkylate amines using alcohols as latent electrophiles. The catalytic system developed here was found to be one of the most active systems reported to date, allowing the reaction to be performed at temperatures as low as 50 °C for the first time. A broad substrate scope was examined. Combined experimental and theoretical studies into the reaction mechanism are consistent with a metal-ligand bifunctional activity of the new catalyst.

An efficient method for the synthesis of beta-hydroxy and beta-amino ketones from allylic alcohols catalyzed by Ru(5-C5Ph5)(CO)2Cl is described. The influence of the stereoelectronic properties of the catalyst on the reaction outcome has been studied. Optimization of the reaction conditions supressed the formation of undesired side products such as saturated ketones, benzyl alcohols, and a,beta-unsaturated ketones. Several aromatic and aliphatic allylic alcohols have been reacted with a large variety of aldehydes or imines to produce beta-hydroxy ketones or beta-amino ketones, respectively, in yields up to 99%. Based on experimental data, a mechanism via ruthenium alkoxides and ruthenium aldoxides is proposed. In addition, a C-bound ruthenium enolate has been characterized.

A series of new iridium(III) complexes containing bidentate N-heterocyclic carbenes (NHC) functionalized with an alcohol or ether group (NHC?OR, R=H, Me) were prepared. The complexes catalyzed the alkylation of anilines with alcohols as latent electrophiles. In particular, biscationic IrIII complexes of the type [Cp*(NHC-OH)Ir(MeCN)]2+2[BF4-] afforded higher-order amine products with very high efficiency; up to >99?% yield using a 1:1 ratio of reactants and 12.5 mol?% of Ir, in short reaction times (216 h) and under base-free conditions. Quantitative yields were also obtained at 50?degrees C, although longer reaction times (4860 h) were needed. A large variety of aromatic amines have been alkylated with primary and secondary alcohols. The reactivity of structurally related iridium(III) complexes was also compared to obtain insights into the mechanism and into the structure of possible catalytic intermediates. The IrIII complexes were stable towards oxygen and moisture, and were characterized by NMR, HRMS, single-crystal X-ray diffraction, and elemental analyses.

C-60 nanorods with hexagonal cross sections are grown using a static liquid-liquid interfacial precipitation method in a system of C-60/m-dichlorobenzene solution and ethanol. Adding water to the ethanol phase leads instead to C-60 tubes where both length and diameter of the C-60 tubes can be controlled by the water content in the ethanol. Based on our observations we find that the diameter of the rods/tubes strongly depends on the nucleation step. We propose a liquid-liquid interface growth model of C-60 rods and tubes based on the diffusion rate of the good C-60 containing solvent into the poor solvent as well as on the size of the crystal seeds formed at the interface between the two solvents. The grown rods and tubes exhibit a hexagonal solvate crystal structure with m-dichlorobenzene solvent molecules incorporated into the crystal structure, independent of the water content. An annealing step at 200 degrees C at a pressure <1 kPa transforms the grown structures into a solvent-free face centered cubic structure. Both the hexagonal and the face centered cubic structures are very stable and neither morphology nor structure shows any signs of degradation after three months of storage.

C-60 nanorods with hexagonal cross sections are grown using a static liquid-liquid interfacial precipitation method in a system of C-60/m-dichlorobenzene solution and ethanol. Adding water to the ethanol phase leads instead to C-60 tubes where both length and diameter of the C-60 tubes can be controlled by the water content in the ethanol. Based on our observations we find that the diameter of the rods/tubes strongly depends on the nucleation step. We propose a liquid-liquid interface growth model of C-60 rods and tubes based on the diffusion rate of the good C-60 containing solvent into the poor solvent as well as on the size of the crystal seeds formed at the interface between the two solvents. The grown rods and tubes exhibit a hexagonal solvate crystal structure with m-dichlorobenzene solvent molecules incorporated into the crystal structure, independent of the water content. An annealing step at 200 degrees C at a pressure <1 kPa transforms the grown structures into a solvent-free face centered cubic structure. Both the hexagonal and the face centered cubic structures are very stable and neither morphology nor structure shows any signs of degradation after three months of storage.

Textile fibers and yarns of high conductivity, and their integration into wearable textiles for different electronic applications, have become an important research field for many research groups throughout the world. We have produced novel electrically conductive textile yarns by vapor-phase polymerization (VPP) of a conjugated polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), on the surface of commercially available textile yarns (viscose). In this article, we have presented a novel setup for electrical resistance measurements, which can be used not only for fibrous structures but also for woven structures of specific dimensions. We have reported a two-point resistance- measuring method using an already manufactured setup and also a comparison with the conventionally used method (so-called crocodile clip method). We found that the electrical properties of PEDOT-coated viscose fibers strongly depend on the concentration of oxidant (FeCl3)and the doping (oxidation) process of PEDOT. To evaluate the results, we used mass specific resistance values of PEDOT-coated viscose yarns instead of normal surface resistance values. The voltage–current (V–I) characteristics support the ohmic behavior of coated fibers to some extent. Monitoring of the charging effect of the flow of current through conductive fibers for prolonged periods of time showed that conductivity remains constant. The change in electrical resistance values with increase in the length of coated fibers was also reported. The resistance measuring setup employed could also be used for continuous measurement of resistance in the production of conductive fibers, as well as for four-point resistance measurement.

Exceptionally high affinity for cesium cations was achieved in aqueous solution using two enantiopure cryptophanes. Complexation of cesium was evidenced by Cs-133 NMR spectroscopy and by electronic circular dichroism (ECD). Binding constants as high as 6 X 10(9) M-1 have been measured by isothermal titration calorimetry (ITC). Very strong complexation of rubidium cations (K similar to 10(6) M-1) has also been measured. Chiral hosts allowed the detection of the two cations at low concentrations (mu M) using ECD.

A detailed mechanistic investigation of the previously reported ruthenium pseudo-dipeptide-catalyzed asymmetric transfer hydrogenation (ATH) of aromatic ketones was performed. It was found that the addition of alkali metals has a large influence on both the reaction rate and the selectivity, and that the rate of the reaction was substantially increased when THF was used as a co-solvent. A novel bimetallic mechanism for the ruthenium pseudo-dipeptide-catalyzed asymmetric reduction of prochiral ketones was proposed.

There is a demand for a larger substrate scope in the ATH reaction, and heteroaromatic ketones are traditionally more challenging substrates. Normally a catalyst is developed for one benchmark substrate, and a substrate screen is carried out with the best performing catalyst. There is a high probability that for different substrates, another catalyst could outperform the one used. To circumvent this issue, a multiple screen was executed, employing a variety of ligands from different families within our group’s ligand library, and different heteroaromatic ketones to fine-tune and to find the optimum catalyst depending on the substrate. The acquired information was used in the formal total syntheses of (R)-fluoxetine and (S)-duloxetine, where the key reduction step was performed with high enantioselectivities and high yield, in each case.

Furthermore, a new iron-N-heterocyclic carbene (NHC)-catalyzed hydrosilylation (HS) protocol was developed. An active catalyst was formed in situ from readily available imidazolium salts together with an iron source, and the inexpensive and benign polymethylhydrosiloxane (PMHS) was used as hydride donor. A set of sterically less demanding, potentially bidentate NHC precursors was prepared. The effect proved to be remarkable, and an unprecedented activity was observed when combining them with iron. The same system was also explored in the reduction of amides to amines with satisfactory results.

A total of 21 amino acid based ligands including hydroxy amide, thioamide, and hydroxamic acid functionalities, respectively, were combined with [Ru(p-cymene)Cl2]2 and [RhCp*Cl2]2, and used as catalysts for the asymmetric transfer hydrogenation of four different heteroaromatic ketones in 2-propanol. The reactions were performed on a Chemspeed automated high-throughput screening robotic platform. Optimal catalysts were identified for the individual heterocyclic substrate classes. Based on these results, the formal syntheses of the antidepressant drugs (R)-fluoxetine and (S)-duloxetine were conducted by using the found catalysts in the key reaction step, which results in high isolated yields (94?%) and excellent product enantioselectivities (>99?% ee) of the formed 1,3-amino alcohols.

Aromatic aldehydes, along with aryl alkyl, heteroaryl alkyl, and dialkyl ketones were efficiently reduced to their corresponding primary and secondary alcohols, respectively, in high yields, using the commercially available and inexpensive polymeric silane, polymethylhydrosiloxane (PMHS), as reducing agent. The reaction is catalyzed by in situ generated iron complexes containing hydroxyethyl-functionalized NHC ligands. Turnover frequencies up to 600 h−1 were obtained

A review. The asym. hydrogenation of olefins is a tremendously powerful tool used to synthesize chiral mols. The field was pioneered using rhodium- and ruthenium- based catalysts; however, catalysts based on both of these metals suffer from limitations, such as the need for directing substituents near or even adjacent to the olefin. Iridium-based catalysts do not suffer from this flaw and can thus hydrogenate a wide variety of olefins, including some tetra substituted ones. It is also possible for iridium-based catalysts to hydrogenate hetero-π bonds such as those found in heteroarom. rings. This review summarizes the contributions made to this field by the authors in the past few years. [on SciFinder(R)]

For biocatalytic production of pharmaceutically important chiral amines the.-transaminase enzymes have proven useful. Engineering of these enzymes has to some extent been accomplished by rational design, but mostly by directed evolution. By use of a homology model a key point mutation in Chromobacterium violaceum omega-transaminase was found upon comparison with engineered variants from homologous enzymes. The variant Trp60Cys gave increased specificity for (S)-1-phenylethylamine (29-fold) and 4'-substituted acetophenones (similar to 5-fold). To further study the effect of the mutation the reaction rates were Swain-Lupton parameterised. On comparison with the wild type, reactions of the variant showed increased resonance dependence; this observation together with changed pH optimum and cofactor dependence suggests an altered reaction mechanism.

A series of novel TIQ based N,N'-oxide ligands were synthesised and screened for their catalytic activity in the enantioselective conjugate addition of thioglycolate to chalcones. Bulky groups on the side chain of the TIQ backbone provided the highest enantioselectivity of up to 88% with 10 mol % catalyst loading. It was also observed that these reactions proceeded optimally in the presence of dichloromethane as a solvent. Screening of various metals emphasized La(OTf)(3) as the ideal pre-catalyst for this particular reaction.

A new iodine-free electrolyte based on amino acids L-cysteine/L-cystine as a redox couple has been designed and synthesized. DSSCs fabricated with the conventional I-/I-3(-) redox couple gave efficiencies of 8.1% and 6.3% under optimized experimental conditions based on ruthenium dye, N719, and metal-free organic dye, TH202, respectively. Based on the same dyes, the DSSCs employing the new L-cysteine/L-cystine redox couple showed comparable efficiencies of 7.7% and 5.6%, respectively. However, higher incident-photon-to-electron (IPCE) conversion efficiencies and larger J(sc) values were found for devices with the L-cysteine/L-cystine redox couple than with I-/I-3(-). From an electrochemical impedance spectroscopic study, we found that the charge recombination between the conduction band electrons in the TiO2 film and the electrolyte containing the L-cysteine/L-cystine redox couple is restrained.

Two new highly modular carbohydrate-based, pseudodipeptide and thioamide ligand libraries have been synthesized for the rhodium- and ruthenium-catalyzed asymmetric transfer hydrogenation (ATH) of prochiral ketones. These series of ligands can be prepared efficiently from easily accessible D-xylose and D-glucose. The ligand libraries contain two main ligand structures (pseudodipeptide and thioamide) that have been designed by making systematic modifications to one of the most successful ligand families developed for the ATH. As well as studying the effect of these two ligand structures on the catalytic performance, we also evaluated the effect of modifying several of the ligand parameters. We found that the effectiveness of the ligands at transferring the chiral information in the product can be tuned by correctly choosing the ligand components (ligand structure and ligand parameters). Excellent enantioselectivities (ees up to 99%) were therefore obtained in both enantiomers of the alcohol products using a wide range of substrates.

An organic dye JY1 bearing a nitro group was designed, synthesized and applied in DSCs. An unusual colour change was observed when the voltage applied to the device was reversed which was accompanied by a five-fold increase in the cell efficiency. We propose that applying a bias enabled the attachment of nitro groups to the TiO2 surface.

The main focus of this thesis is on the aromaticity of the ground state and electronically excited states of π-conjugated molecules and polymers, as well as how aromaticity is connected to their properties.

The electronic structures of polybenzenoid hydrocarbons (PBHs) were explored through density functional theory (DFT) calculations and the π-component of the electron localization function (ELFπ). The study revealed how the π-electronic structure is influenced by the fusion of double bonds or benzene rings to the PBHs. We also demonstrated that the π-electrons of benzene extend to accommodate as much aromaticity as possible when bond length distorted.

The aromatic chameleon property displayed by fulvenes, isobenzofulvenes, fulvalenes, bis(fulvene)s, and polyfulvenes were investigated using DFT calculations. The tria-, penta-, and heptafulvenes were shown to possess ionization energies and electron affinities which can be tuned extensively by substitution, some of which even outperform TTF and TCNQ, the prototypical electron donor and acceptor, respectively. The singlet-triplet energy gap of pentafulvenes can be tuned extensively by substitution to the point that the triplet state is lower than the singlet state and thus becomes the ground state. The ELFπ of isobenzofulvene shows that the benzene ring in an electronically excited state can be more aromatic than the corresponding ring in the ground state. We have shown that the 6-ring of [5.6.7]quinarene is influenced by a Hückel aromatic resonance structure with 4n+2 π-electrons in the excited quintet state. The bis(fulvene)s which are composed of a donor type heptafulvene and an acceptor type pentafulvene, retain the basic donor-acceptor properties of the two fragments and could function as compact donor-acceptor dyads. A few of the designed polyfulvenes were found to have band gaps below 1 eV at the PBC-B3LYP/6-31G(d) level.

Various 2,7-disubstituted fluorenones and dibenzofulvenes were synthesized and their excited state properties were investigated by absorption spectroscopy and time-dependent DFT calculations. It was found that the 1A → 1B transition of ππ* character can be tuned by substitution in the 2,7-positions. The 2,7-bis(N,N-dimethyl) derivatives of fluorenone and dibenzofulvene displayed low energy transitions at 2.18 and 1.61 eV, respectively, in toluene.

The singlet ground states and lowest triplet states of penta- and heptafulvene, their benzannulated derivatives, as well as the lowest quintet states of pentaheptafulvalenes, either the parent compound or compounds in which the two rings are intercepted by either an alkynyl or a phenyl segment, were investigated at the (U)OLYP/6-311G(d,p) density functional theory level. The influence of (anti)-aromaticity was analyzed by the structure-based aromaticity index HOMA, the harmonic oscillator model of aromaticity. The extent of (anti)aromatic character was also evaluated in terms of the pi-electron (de)localization as measured by the pi component of the electron localization function (ELF pi). The natural atomic orbital (NAO) occupancies were calculated in order to evaluate the degree of pi-electron shift caused by the opposing electron-counting rules for aromaticity in the electronic ground state (S-0; Hiickel's rule) and the first pi pi* excited triplet state (T-1; Baird's rule). Pentaheptafulvalene (5) shows a shift of 0.5 pi electrons from the 5-ring to the 7-ring when going from the S-0 state to the lowest quintet state (Qu(1)). The pentaheptafulvalene 5 and [5.6.7]quinarene 7 were also investigated in their 90 degrees twisted conformations. From our study it is apparent that excitation localization in fulvalenes, but not in fulvenes, to a substantial degree is determined by aromaticity localization to triplet biradical 4n pi-electron cycles. Isolated benzene rings in these compounds tend to remain as closed-shell 6 pi-electron cycles.

This thesis deals with the development of new reaction methodology as well as stereochemical investigations.

The first part concerns the investigation of 1,2- and merged 1,2- and 1,3- asymmetric induction in Mukaiyama aldol additions to α-heteroatom and α,β- heteroatom substituted aldehydes respectively. In particular, the unexpected 1,2-syn selectivity obtained in the addition of sterically hindered nucleophiles to α-chloroaldehydes is examined, and an explanation for the observed stereochemical trends is proposed.

The second part describes the development of a novel entry to α-amino-β- hydroxy esters by a 1,3-dipolar cycloaddition reaction of aldehydes and azomethine ylides, generated by thermolysis of aziridines.

The third part deals with our efforts to develop a novel entry to vicinal all- carbon quaternary centers, based on an intramolecular domino Heck- carbonylation reaction using tetrasubstituted olefins.

The concept of combining heterogeneous transition metal and amine catalysis for enantioselective cascade reactions has not yet been realized. This is of great advantage since it would allow for the recycling of expensive and non-environmentally friendly transition metals. We disclose that the use of a heterogeneous Pd-catalyst in combination with a simple chiral amine co-catalyst allows for highly enantioselective cascade transformations. The preparative power of this process has been demonstrated in the context of asymmetric cascade Michael/carbocyclization transformations that delivers cyclopentenes bearing an all carbon quaternary stereocenters in high yields with up to 30: 1 dr and 99% ee. Moreover, a variety of highly enantioselective cascade hetero-Michael/carbocyclizations were developed for the one-pot synthesis of valuable dihydrofurans and pyrrolidines (up to 98% ee) by using bench-stable heterogeneous Pd and chiral amines as co-catalysts.

A highly enantioselective, metal-free cascade reaction between di-1,2-N-protected hydrazine and α,β-unsaturated aldehydes is disclosed. The catalytic, asymmetric cascade transformation is a direct entry to 3-hydroxypyrazolidine and 3-allylpyrazolidine derivatives in one step and two steps, respectively, with >19:1 d.r. and 98–99 % ee using simple chiral pyrrolidines as catalysts.

The carbonium ion has been suggested to be the intermediate in superacid-promoted reactions (SbF5-HF) such as hydrogen-deuterium exchange and in the electrophilic C-H cleavage into hydrogen and the carbenium ion. In this study, the superacid-promoted C-H cleavage into hydrogen and the carbenium ion was studied using density functional theory (B3LYP and M062X) and ab initio methods (MP2 and CCSD). The calculations suggest that the superacid-promoted C-H cleavage proceeds via a concerted transition state leading to hydrogen (H-2) and the carbenium ion without the formation of the elusive carbonium ion. The reactivity for the superacid promoted C-H cleavage decreases upon going from isobutane (tertiary) > propane (secondary) > isobutane (primary) > propane (primary) > ethane >> methane.

An efficient synthesis of formylacetic esters via ozonolysis of trans-beta-hydromuconic esters followed by a solid-supported triphenylphosphine reduction has been developed. In addition, an extension toward formylacetic amides and a one-pot preparation of more stable intermediates which can be used for further transformations are also described.

Enzymes are attractive catalysts in organic synthesis since they are efficient, selective and environmentally friendly. A large number of enzyme-catalyzed transformations have been described in the literature. If no natural enzyme can carry out a desirable reaction, one possibility is to modify an existing enzyme by protein engineering and thereby obtain a catalyst with the desired properties. In this thesis, the development of enantioselective enzymes and their use in synthetic applications is described.

In the first part of this thesis, enantioselective variants of Candida antarctica lipase A (CALA) towards α-substituted p-nitrophenyl esters were developed by directed evolution. A highly selective variant of CALA towards p-nitrophenyl 2-phenylpropanoate was developed by pairwise randomization of amino acid residues close to the active site. The E value of this variant was 276 compared to 3 for the wild type.

An approach where nine residues were altered simultaneously was used to discover another highly enantioselective CALA variant (E = 100) towards an ibuprofen ester. The sterical demands of this substrate made it necessary to vary several residues at the same time in order to reach a variant with improved properties.

In the second part of the thesis, a designed variant of Candida antarctica lipase B (CALB) was employed in kinetic resolution (KR) and dynamic kinetic resolution (DKR) of secondary alcohols. The designed CALB variant (W104A) accepts larger substrates compared to the wild type, and by the application of CALB W104A, the scope of these resolutions was extended.

First, a DKR of phenylalkanols was developed using CALB W104A. An enzymatic resolution was combined with in situ racemization of the substrate, to yield the products in up to 97% ee. Secondly, the KR of diarylmethanols with CALB W104A was developed. By the use of diarylmethanols with two different aryl groups, highly enantioselective transformations were achieved.

An enzymatic kinetic resolution of diarylmethanols via acylation has been developed. This was achieved by the use of a mutated variant of CALB that accepts larger substrates compared to the wild type. By the use of diarylmethanols with two differently sized aryl groups, enantioselective transformations were achieved. A larger size-difference led to a higher enantioselectivity. In addition, substrates with electronically different aryl groups, such as phenyl and pyridyl, also gave an enantioselective reaction. The highest E value was observed with a substrate where steric and electronic effects were combined.

The title compound, C13H24O10·4H2O, is the methyl glycoside of a disaccharide structural element present in the backbone of the capsular polysaccharide from Klebsiella K1, which contains only three sugars and a substituent in the polysaccharide repeating unit. The conformation of the title disaccharide is described by the glycosidic torsion angles ϕH = 51.1 (1)° and ψH = 25.8 (1)°. In the crystal, a number of O—HO hydrogen bonds link the methyl glycoside and water mol­ecules, forming a three-dimensional network. One water mol­ecule is disordered over two positions with occupancies of 0.748 (4) and 0.252 (4).

The title hydrate, C19H34O13·5H2O, contains a vicinally disubstituted tris­accharide in which the two terminal rhamnosyl sugar groups are positioned adjacent to each other. The conformation of the tris­accharide is described by the glycosidic torsion angles ϕ2 = 48 (1)°, ψ2 = −29 (1)°, ϕ3 = 44 (1)° and ψ3 = 4 (1)°, whereas the ψ2 torsion angle represents a conformation from the major state in solution, the ψ3 torsion angle conformation may have been caught near a potential energy saddle-point when compared to its solution structure, in which at least two but probably three conformational states are populated. Extensive inter­molecular O—HO hydrogen bonding is present in the crystal and a water-containing channel is formed along the b-axis direction.

The structure of the repeating unit of the O-antigenic polysaccharide (PS) from Escherichia coli O174 has been determined. Component analysis together with H-1 and C-13 NMR spectroscopy experiments were employed to elucidate the structure. Inter-residue correlations were determined by H-1, C-13-heteronuclear multiple-bond correlation and H-1, H-1-NOESY experiments. The PS is composed of tetrasaccharide repeating units with the following structure: -> 4)-beta-D-GlcpA-(1 -> 3)-beta-D-Galp-(1 -> 3)-beta-D-GalpNAc-(1 -> vertical bar beta-D-GlcpNAc-(1 -> 2) Cross-peaks of low intensity were present in the NMR spectra consistent with a beta-D-GlcpNAc-(1 -> 2)-beta-D-GlcpA(1 -> structural element at the terminal part of the polysaccharide, which on average is composed of similar to 15 repeating units. Consequently the biological repeating unit has a 3-substituted N-acetyl-D-galactosamine residue at its reducing end.

Electric breakdown in power transformers is preceded by pre-breakdown events such as streamers. The understanding of these phenomena is important in order to optimize liquid insulation systems. Earlier works have derived a model that describes streamers in transformer oil and utilized a finite element method to produce numerical solutions. This research investigates the consequences of changing the numerical method to a finite volume-based solver implemented in OpenFOAM. Using a standardized needle-sphere geometry, a number of oil and voltage combinations were simulated, and the results are for the most part similar to those produced by the previous method. In cases with differing results the change is attributed to the more stable numerical performance of the OpenFOAM solver. A proof of concept for the extension of the simulation from a two-dimensional axial symmetry to three dimensions is also presented.

Four novel tetrahydroquinoline dyes by inserting isophorone and/or thiophene moieties as pi bridge between the electron donating unit of substituted tetrahydroquinoline and the electron withdrawing unit of cyano carboxylic acid have been synthesized and successfully applied to dye-sensitized solar cells. Among them, DSCs sensitized by HYTIC, which shows the simplest molecular structure, exhibit improved efficiency of 7.0%. This by now is the highest efficiency for the reported tetrahydroquinoline sensitizers and comparable to the performance of N719-sensitized solar cells under the conditions employed here. (C) 2011 Elsevier Ltd. All rights reserved.

The physicochemical properties of gold nanoparticles (GNPs) functionalized with peptides and N-methylated peptides were studied with respect to their interaction with beta-amyloid (1-42). Peptides with sequences of CGGIGLMVG and CGGGGGIGLMVG linked with GNPs of an average diameter of 13 nm were employed for this study. The peptide-GNPs were found to be soluble and dispersed at pH 7.4 in a sodium phosphate aqueous buffer solution. The resonance spectra of each peptide coated GNP was measured in the absence and presence of beta-amyloid (1-42). The difference in the intensity of the lambda(max) of the resonance absorption bands was attributed to the interaction of the functionalized GNPs with the protein. Particles bearing the CGGGGGIGLMVG sequence exhibited the largest change in lambda(max) intensity; the prevention of fibril formation and inhibition of cytotoxicity was also examined.

50.

Hillgren, J Mikael

et al.

Umeå University, Faculty of Science and Technology, Department of Chemistry.

Öberg, Christopher T

Umeå University, Faculty of Science and Technology, Department of Chemistry.

Elofsson, Mikael

Umeå University, Faculty of Science and Technology, Department of Chemistry.

Herein we report the total syntheses of pseudoceramine A-D (2-5) and spermatinamine (1) isolated from the marine sponge Pseudoceratina sp. Direct acyl substitution of α-hydroxyiminoesters with amine nucleophiles was developed as a key transformation. The synthetic compounds confirm the reported structures and importantly gives access to non-symmetrical spermine based natural products carrying two different bromotyrosine building blocks. Our new synthesis of spermatinamine is two steps shorter and more efficient than the previously reported sequence.